1-Hydroxy-2-naphthoic acid → HCID 23132830、化合物

8.0 g of Wang resin (loading: 1.4 mmol/g) was placed in a solid phase fritted reaction vessel with 75 ml of dimethylformamide. After 5 minutes of swelling, 7.01 ml, of N,N′-diisopropyl carbodiimide, 0.136 g of 4-dimethylaminopyridine and 14.58 g of 2-(9H-Fluoren-9-ylmethoxy-carbonylamino)-2-methyl-propionic acid were added. The reaction was placed in an orbital shaker for 2 days, after which it was filtered, washed 4 times each with dimethylformamide, methanol and dichloromethane. Next, the resin was swollen in 50 ml of dichloromethane, 5.26 ml of acetic anhydride and 19.5 ml of N,N-diisopropylethylamine were added (to cap any unreacted hydroxyl group). It was filtered, washed 4 times each with dimethylformamide, methanol and dichloromethane and dried in vacuo. The loading was checked using a Perkin Elmer UV instrument (Fmoc-Echo test) to give 0.71 mmol/g(theoretical: 0.98 mmol/g). To 11 g (0.71 mmol/g) of the Wang-resin carrying Fmoc-2-Amino-2-methyl-propionic acid was added 140 ml of 20% piperidine in dimethylformamide. It was left in the orbital shaker for 1 hour, after which it was washed four times each with dimethylformamide, methanol and dichloromethane and dried in vacuo. To this Fmoc-deproteced resin was added 150 ml of dimethylformamide, 6.34 ml (40.5 mmol) of N,N′-diisopropyl carbodiimide, 7.62 g of 1-hydroxy-2-naphthoic acid and 5.47 g of 1-hydroxy-benzotriazole. The solid phase reaction was left 2 days in an orbital shaker. Since the reaction was not complete by resin colorimetric tests (Bromophenol blue test for presence of primary amines), once filtered, the same amounts of reagents were re-added to the resin and placed in a flex rotating oven for 4 hours at 55° C. and then left overnight at room temperature. Then it was filtered, washed four times each with dimethylformamide, methanol and dichloromethane and dried in vacuo. (Bromophenol blue test was negative). 10 g of the Wang-resin-bound 2-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid were obtained.

1. waitThe reaction was placed in an orbital shaker for 2 days
2. filtrationafter which it was filtered
3. washwashed 4 times each with dimethylformamide, methanol and dichloromethane
4. addition5.26 ml of acetic anhydride and 19.5 ml of N,N-diisopropylethylamine were added (
5. customto cap any unreacted hydroxyl group)
6. filtrationIt was filtered
7. washwashed 4 times each with dimethylformamide, methanol and dichloromethane
8. customdried in vacuo
9. customto give 0.71 mmol/g(theoretical: 0.98 mmol/g)
10. waitIt was left in the orbital shaker for 1 hour
11. washafter which it was washed four times each with dimethylformamide, methanol and dichloromethane
12. customdried in vacuo
13. customThe solid phase reaction
14. waitwas left 2 days in an orbital shaker
15. filtrationonce filtered
16. additionthe same amounts of reagents were re-added to the resin
17. customfor 4 hours
18. customat 55° C.
19. waitleft overnight at room temperature
20. filtrationThen it was filtered
21. washwashed four times each with dimethylformamide, methanol and dichloromethane
22. customdried in vacuo

ORDレコード

ord-ec193e581cbc447980ab0d89ba338c25

出典データセット

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08283479B2